The most common techniques for studying cell populations are flow cytometry and fluorescence microscopy. Flow cytometry is particularly powerful in that it affords the ability to rapidly evaluate large numbers of cells at the single-cell level. Unfortunately, flow cytometry is limited in that cells must be in suspension for analysis, which often requires enzymatic stripping of adherent cells from the surface they are cultured on. Fluorescence microscopy is thus a useful alternative, as it facilitates the evaluation of adherent cells in situ. But analysis by microscopy also causes significant perturbation through the loading of high concentrations of fluorescent dyes, and (in many cases) through the toxic process of permeabilization and fixation.
An alternative to flow cytometry and fluorescence microscopy for analyzing the behavior of adherent cells is impedance analysis. In this method, a layer of cells is grown on the surface of a micropatterned electrode and is exposed to low-magnitude AC voltage. Current then flows between the cells such that the impedance is correlated with cell number, and capacitatively couples through the cells such that the impedance is correlated with cell type and state. This method is growing in popularity, as it enables real-time analysis of cells in culture without the need for enzymatic stripping, fluorescent dyes, fixatives, or other perturbations.
A limitation for most cell impedance measurement systems relative to flow cytometry and microscopy is throughput. Typically, cell impedance analysis systems are integrated in multiwell plate format; e.g., the Applied Biophysics ECIS® system. In laboratories lacking robotic dispensers and aspirators, this forms a practical limit to the throughput that is achievable. Moreover, such techniques require significant cell and reagent use, making them cost-prohibitive for many researchers.